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asthma pathophysiology

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https://www.readbyqxmd.com/read/27906698/ige-and-eosinophils-as-therapeutic-targets-in-asthma
#1
Tanvi R Patel, Sanjiv Sur
PURPOSE OF REVIEW: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27905186/severe-asthma-current-management-targeted-therapies-and-future-directions-a-roundtable-report
#2
REVIEW
Vanessa M McDonald, Steven Maltby, Helen K Reddel, Gregory G King, Peter A B Wark, Lorraine Smith, John W Upham, Alan L James, Guy B Marks, Peter G Gibson
Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1-5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5-10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden...
November 30, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27899696/selective-antagonism-of-trpa1-produces-limited-efficacy-in-models-of-inflammatory-and-neuropathic-induced-mechanical-hypersensitivity-in-rats
#3
Sonya G Lehto, Andy D Weyer, Beth D Youngblood, Maosheng Zhang, Ruoyuan Yin, Weiya Wang, Yohannes Teffera, Melanie Cooke, Cheryl L Stucky, Laurie Schenkel, Stephanie Geuns-Meyer, Bryan D Moyer, Kenneth D Wild, Narender R Gavva
The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27894811/critical-role-of-toll-like-receptors-in-pathophysiology-of-allergic-asthma
#4
Seyyed Shamsadin Athari, Seyyede Masoume Athari, Fateme Beyzay, Masoud Movassaghi, Esmaeil Mortaz, Mehdi Taghavi
Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species...
November 26, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27872847/strengths-pitfalls-and-lessons-from-longitudinal-childhood-asthma-cohorts-of-children-followed-up-into-adult-life
#5
REVIEW
Andrew Tai
Asthma is a common problem worldwide and longitudinal studies of children followed up into adult life enable the assessment of clinical outcomes, examine the pattern of lung function outcomes, and importantly provide insight into aetiology and prognosis for patients with asthma. The aim of this review is to examine the major childhood asthma cohort studies which have continued into adult life, describing the strengths and weaknesses and the lessons that can be learnt regarding pathophysiology and potential future directions for research...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27867084/new-concepts-in-asthma-clinical-phenotypes-and-pathophysiological-mechanisms
#6
REVIEW
Andreas R Koczulla, Claus F Vogelmeier, Holger Garn, Harald Renz
Asthma is among the most common chronic inflammatory diseases worldwide. Recent evidence indicates that the pathogenesis shows a high degree of heterogeneity. Patient subsets have been identified that exhibit different cellular and molecular patterns of dysregulation. A prominent example is eosinophilic Th2-driven asthma. These unique and molecular patterns are termed endotypes. Characterization of endotypes has broad implications for therapeutic interventions. Although ∼80% of asthmatic patients respond well to standard anti-inflammatory therapies, the remaining subset particularly consisting of severe patients requires a more specialized endotype-specific approach...
November 17, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27856660/effect-of-il-17-receptor-a-blockade-with-brodalumab-in-inflammatory-diseases
#7
REVIEW
Ajay Nirula, Jon Nilsen, Paul Klekotka, Greg Kricorian, Ngozi Erondu, Jennifer E Towne, Chris B Russell, David A Martin, Alison L Budelsky
IL-17 cytokines are expressed by a variety of cells and mediate host defence against extracellular pathogens. IL-17 is upregulated at sites of inflammation and can synergize with other cytokines, such as TNF-α, to amplify the inflammatory response. Activation of these signalling pathways has been hypothesized to contribute to the underlying pathogenesis of several inflammatory diseases, including psoriasis, RA, PsA and asthma. Thus the IL-17 signalling pathway is an attractive target for the development of therapeutic agents to modulate aberrant inflammatory responses...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27842596/integrative-analysis-of-genetic-data-sets-reveals-a-shared-innate-immune-component-in-autism-spectrum-disorder-and-its-co-morbidities
#8
Sumaiya Nazeen, Nathan P Palmer, Bonnie Berger, Isaac S Kohane
BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that tends to co-occur with other diseases, including asthma, inflammatory bowel disease, infections, cerebral palsy, dilated cardiomyopathy, muscular dystrophy, and schizophrenia. However, the molecular basis of this co-occurrence, and whether it is due to a shared component that influences both pathophysiology and environmental triggering of illness, has not been elucidated. To address this, we deploy a three-tiered transcriptomic meta-analysis that functions at the gene, pathway, and disease levels across ASD and its co-morbidities...
November 14, 2016: Genome Biology
https://www.readbyqxmd.com/read/27836433/sex-differences-in-the-epidemiology-clinical-features-and-pathophysiology-of-migraine
#9
REVIEW
Kjersti Grøtta Vetvik, E Anne MacGregor
Migraine is two to three times more prevalent in women than men, and women report a longer attack duration, increased risk of headache recurrence, greater disability, and a longer period of time required to recover. Conditions recognised to be comorbid with migraine include asthma, anxiety, depression, and other chronic pain conditions, and these comorbidities add to the amount of disability in both sexes. Migraine-specifically migraine with aura-has been identified as a risk factor for vascular disorders, particularly in women, but because of the scarcity of data, the comparative risk in men has yet to be established...
November 8, 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27824862/delayed-type-hypersensitivity-to-metals-of-environmental-burden-in-patients-with-takotsubo-syndrome-is-there-a-clinical-relevance
#10
Jan Manousek, Vera Stejskal, Petr Kubena, Jiri Jarkovsky, Petr Nemec, Petr Lokaj, Ludmila Dostalova, Andrea Zadakova, Marie Pavlusova, Klara Benesova, Petr Kala, Roman Miklik, Jindrich Spinar, Jiri Parenica
OBJECTIVE: Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®...
2016: PloS One
https://www.readbyqxmd.com/read/27818326/an-update-on-lymphocyte-subtypes-in-asthma-and-airway-disease
#11
REVIEW
Daniel M Moldaver, Mark Larché, Christopher D Rudulier
Inflammation is a hallmark of many airway diseases. Improved understanding of the cellular and molecular mechanisms of airway disease will facilitate the transition in our understanding from phenotypes to endotypes, thereby improving our ability to target treatments based on pathophysiology. For example, allergic asthma has long been considered to be driven by an allergen-specific Th2 response. However, clinical and mechanistic studies have begun to shed light on the role of other cell subsets in the pathogenesis and regulation of lung inflammation...
November 3, 2016: Chest
https://www.readbyqxmd.com/read/27817211/asthma-phenotypes-in-childhood
#12
Matea Deliu, Danielle Belgrave, Matthew Sperrin, Iain Buchan, Adnan Custovic
Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes...
November 18, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27815255/chronic-allergic-pulmonary-inflammation-is-aggravated-in-angiotensin-1-7-mas-receptor-knockout-mice
#13
Giselle Santos Magalhães, Maria da Glória Rodrigues-Machado, Daisy Motta-Santos, Natalia Alenina, Michael Bader, Robson Augusto Souza Santos, Luciola S Barcelos, Maria José Campagnole-Santos
Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor pathway is currently recognized as a counterbalancing mechanism of the renin-angiotensin system in different pathophysiological conditions. We have previously described that treatment with Ang-(1-7) attenuates lung inflammation and remodeling in an experimental model of asthma. In the present study, we investigated whether lack of Mas receptor could alter the inflammatory response in a model of chronic allergic lung inflammation induced by ovalbumin (OVA). MasWT and MasKO mice were subjected to 4 doses of OVA (20µg/mice, i...
November 4, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27793419/biochemical-and-physiological-effects-from-exhaust-emissions-a-review-of-the-relevant-literature
#14
REVIEW
Sergio Manzetti, Otto Andersen
Exhaust emissions are to date ranked among the most frequent causes of premature deaths worldwide. The combustion of fuels such as diesel, gasoline, and bio-blends provokes a series of pathophysiological responses in exposed subjects, which are associated with biochemical and immunological triggering. It is critical to understand these mechanisms, which are directly related to the levels of aerosol, liquid and gaseous components in fuel exhaust (e.g. nanoparticles, particulate matter, volatile compounds), so to cast attention on their toxicity and gradually minimize their use...
October 20, 2016: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/27784618/benomyl-induced-effects-of-ormdl3-overexpression-via-oxidative-stress-in-human-bronchial-epithelial-cells
#15
Yoonjeong Jang, Ah Young Lee, Ji-Eun Kim, Sang-Hee Jeong, Jun Sung Kim, Myung-Haing Cho
The respiratory system is a major site of exposure route during pesticide use. Although pesticide exposure is associated with chronic respiratory diseases including asthma, the underlying pathophysiological mechanism remains to be elucidated. In this study, we investigated the in vitro effects of benomyl-induced ORMDL3 overexpression on the toxicological mechanism using the human bronchial epithelial cell line 16HBE14o-. Benomyl increased reactive oxygen species and Ca(2+) levels, and asthma-related ADAM33 and ORMDL3 expression in 16HBE14o- cells...
October 23, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27776981/asthma-metabolomics-and-the-potential-for-integrative-omics-in-research-and-the-clinic
#16
Rachel S Kelly, Amber Dahlin, Michael J McGeachie, Weiliang Qiu, Joanne Sordillo, Emily S Wan, Ann Chen Wu, Jessica Lasky-Su
Asthma is a complex disease well suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma and serum could identify asthmatics and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology and population age...
October 21, 2016: Chest
https://www.readbyqxmd.com/read/27755161/role-of-microbiome-in-the-pathophysiology-and-disease-course-of-asthma
#17
Aran Singanayagam, Andrew I Ritchie, Sebastian L Johnston
PURPOSE OF REVIEW: The emergence of next-generation 16S rRNA sequencing techniques has facilitated a more detailed study of the body's microbiota and led to renewed interest in the association between microbial exposure and asthma inception. In this review, we evaluate the evidence that the respiratory tract and intestinal microbiota contribute to asthma pathogenesis and progression. RECENT FINDINGS: Human studies have revealed associations between the presence of potentially pathogenic bacteria in the respiratory tract in early life and subsequent risk of allergic sensitization and asthma...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27749682/dimensions-of-socioeconomic-status-and-childhood-asthma-outcomes-evidence-for-distinct-behavioral-and-biological-associations
#18
Edith Chen, Madeleine U Shalowitz, Rachel E Story, Katherine B Ehrlich, Cynthia S Levine, Robin Hayen, Adam K K Leigh, Gregory E Miller
OBJECTIVES: The objective of this study was to investigate 2 key dimensions of socioeconomic status (SES)-prestige and resources-and their associations with immune, behavioral, and clinical outcomes in childhood asthma. METHODS: Children ages 9 to 17 years with a physician's diagnosis of asthma (N = 150), and one of their parents participated in this study. Children and parents completed interviews and questionnaires about SES (prestige = parent education; resources = family assets), environmental exposures, and clinical asthma measures...
November 2016: Psychosomatic Medicine
https://www.readbyqxmd.com/read/27746262/caffeic-acid-phenethyl-ester-alleviates-asthma-by-regulating-the-airway-microenvironment-via-the-ros-responsive-mapk-akt-pathway
#19
REVIEW
Yuan Ma, Jia-Xiang Zhang, Ya-Nan Liu, Ai Ge, Hao Gu, Wang-Jian Zha, Xiao-Ning Zeng, Mao Huang
In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments...
October 13, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27746241/intraepithelial-neutrophils-in-pediatric-severe-asthma-are-associated-with-better-lung-function
#20
Cecilia K Andersson, Alexandra Adams, Prasad Nagakumar, Cara Bossley, Atul Gupta, Daphne De Vries, Afiqah Adnan, Andrew Bush, Sejal Saglani, Clare M Lloyd
BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in pediatric asthma is unknown. OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA). METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4...
October 13, 2016: Journal of Allergy and Clinical Immunology
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